ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1597776
This article is part of the Research TopicNeuroinflammation: Mechanisms and Therapeutic InterventionsView all 10 articles
Zika virus induces monocyte recruitment in the immunocompetent adult brain driving chronic inflammation
Provisionally accepted
- University of Virginia, Charlottesville, United States
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Zika virus (ZIKV) is a neurotropic pathogen linked to neuropathogenesis in adults, causing conditions such as Guillain-Barré syndrome (GBS) and fatal encephalitis. Intracranial injection of virus in immunocompromised mice have shown neuroinflammation and subsequent brain damage. However, the mechanisms underlying ZIKV-induced neuroinflammation in immunocompetent adult mice via peripheral infection remain unclear. To investigate this, we utilized a murine model of ZIKV infection via footpad injection. Our findings reveal that acute ZIKV infection at 4 days post-infection (4 dpi) induces significant apoptosis and neuroinflammation in the adult brain, persisting up to 28 dpi. Notably, ZIKV infection triggers apoptosis in the hippocampus and cortex—key regions involved in memory—and induces early immune cell infiltration. Additionally, microglial activation occurs following infection at 7 dpi, with viral RNA detected in the brain. Bulk RNA sequencing of the hippocampus at 28 dpi further reveals the activation of inflammatory pathways, underscoring the prolonged neuroinflammatory response in the infected brain. Microglial activation is likely driven by infiltrating monocytes, as inhibiting monocyte recruitment reduced the expression of microglial activation genes. These results suggest that targeting monocyte-induced inflammatory mediators could be potential therapeutic interventions for ZIKV.
Keywords: Zika (ZIKV), Monocytes, Microglia, neuroinflamamation, Immunocompetent adult brain
Received: 21 Mar 2025; Accepted: 18 Jun 2025.
Copyright: © 2025 Garcia Diaz, Park, Legouez, Comlekoglu, Beck, Kuan and Hahn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Young S Hahn, University of Virginia, Charlottesville, United States
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